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GAT-1 acts to limit a tonic GABAA current in rat CA3 pyramidal neurons at birth


Dr Sampsa T. Sipilä, as above.
E-mail: Sampsa.Sipila@Helsinki.Fi


Tonic activation of GABAA receptors takes place before the development of functional synapses in cortical structures. We studied whether inefficient GABA uptake might explain the presence of a tonic GABAA-mediated current (IGABA-A) in early postnatal hippocampal pyramidal neurons. The data show, however, that the tonic IGABA-A is enhanced by the specific blocker of GABA transporter-1 (GAT-1), NO-711 (1-[2-[[(Diphenylmethyleneimino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), at birth in rat CA3 pyramidal neurons. NO-711 also prolonged the duration of GABA transients during endogenous hippocampal network events (known as giant depolarizing potentials) at postnatal day 0. The endogenous tonic IGABA-A was seen and it was enhanced by NO-711 in the presence of tetrodotoxin, which itself had only a minor effect on the holding current under control conditions. This indicates that the source of interstitial GABA is largely independent of action-potential activity. The tonic IGABA-A in neonatal CA3 pyramidal neurons was increased by zolpidem, indicating that at least a proportion of the underlying GABAA receptors contain γ2 and α1–α3 subunits. The present data point to a significant role for GAT-1 in the control of the excitability of immature hippocampal neurons and networks.